The fundamental goal of this project is to establish a hovel, spontaneous, inherited feline model for human glaucoma research. A viable breeding colony has been established and we have determined that this form of feline glaucoma is inherited as an autosomal recessive trait. This proposal outlines a five-year plan to conduct rigorous clinical, functional and morphological characterization of primary glaucoma within this pedigree of cats. Over the first 3 years of the project, a cohort of cats will be evaluated longitudinally by both non-invasive means (including tonometry, high resolution ultrasonography, fluorophotometry, optical coherence tomography and electrophysiology) and by histomorphological evaluation of retinal and optic nerve pathology, in order to characterize the natural history of disease progression and establish structure function correlations. In the final years of the project we will begin to examine the outcomes of intraocular pressure-lowering as a neuroprotective treatment strategy on disease progression in a further cohort of cats. Results of the proposed studies will provide clues as to the complex patho-physiological basis of glaucoma and will address a number of key research priorities of the NEI's research program in glaucoma and optic neuropathies. The candidate of this proposal is a veterinarian with prior clinical and PhD training in the field of comparative ophthalmology. This research project will provide a framework for a training program, under the mentorship of leading researchers in their respective fields, which will afford the candidate the opportunity to gain new laboratory research skills as well as further training in the ethical, responsible and efficient conduct of research. The proposed training program will provide the candidate with a strong background in glaucoma research and serve as the foundation for a career as an academic veterinary clinician and independent researcher. Glaucoma is an important cause of vision loss in the human population. The development of effective treatment strategies for glaucoma patients is currently hampered by a lack of accessible, well-characterized, large animal models. Once characterized, this model will represent a valuable resource for other investigators and will facilitate the translation of laboratory research findings into new clinical strategies for the early detection and more effective treatment of this disabling disease in human patients. [unreadable][unreadable]